Methyl iodide → HCID 59242018, compound

HRID 1876210Notes

Reaction equation

HRID 1876210 reaction equation
Cl[CH2:2][C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.Cl.ClCC1N=C(NC2C=CC(OC)=C(F)C=2)C2C(=CC=CC=2)[N:28]=1.CI.[H-].[Na+]>C1COCC1>[NH2:28][CH2:2][C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68517283HCID 68517283, compoundHCID 68518549HCID 68518549, compound

Product 1

HCID 59242018HCID 59242018, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2-Chloromethyl-quinazolin-4-yl)-(3-fluoro-4-methoxy-phenyl)-methyl-amine: A suspension of (2-chloromethyl-quinazolin-4-yl)-(3-fluoro-4-methoxy-phenyl)-amine hydrochloride (497 mg, 1.4 mmol) and MeI (0.18 mL, 2.9 mmol) in THF (7 mL) was treated with NaH (60% disp., 158 mg, 3.95 mmol) and stirred for 2 h at rt. The reaction was quenched by the addition of MeOH, concentrated onto SiO2 and purified by gradient MPLC (SiO2, EtOAc/hexanes, 0-100%) to provide 281 mg (61%) of the title compound. 1H NMR (CDCl3) δ 7.85 (d, 1H), 7.61 (ddd, 1H), 6.97-7.13 (m, 3H), 6.86-6.97 (m, 2H), 4.75 (s, 2H), 3.93 (s, 3H), 3.62 (s, 3H); LC-MS (ESI+; 332 ([M+H]+)).

Workup

  1. customThe reaction was quenched by the addition of MeOH
  2. concentrationconcentrated onto SiO2
  3. custompurified by gradient MPLC (SiO2, EtOAc/hexanes, 0-100%)

Sources & evidence

ORD record
ord-1c8d3d8225eb4638840ede99f7a54c37
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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